O-methylation with trimethyl orthoacetate
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
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(17), 220 (8), 207 (18), 204 (11), 202 (11), 189 (15), 179 (14), 149
(22), 69 (42), 45 (12), 44 (26), 43 (100), 42 (8), 41 (25), 32 (82).
2,5,8-Trihydroxy-6-methoxy-1,4-naphthoquinone (13). Yield
59%, m.p. 226—228 C (cf. Ref. 23: 224—226 C; Ref. 40:
265—267 C). IR (CDCl3), /cm–1: 3600—2200 (-OH), 3512
(-OH), 3392 (-OH), 2991, 2942, 2866, 2832, 1628, 1602, 1582.
1H NMR (CDCl3), : 3.99 (s, 3 H, OMe); 6.41, 6.47 (both s,
1 H each, H(3), H(7)); 7.38 (br.s, 1 H, C(2)OH), 12.25, 13.30 both s,
1 H each, C(8)OH, C(5)OH). 13C NMR (CDCl3), : 56.91
(OMe); 105.43 (C(7)); 105.82 (C(8a)); 109.72 (C(4a)); 110.07
(C(3)); 157.96 (C(2)); 161.00 (C(6), C(8)); 167.72 (C(5)); 172.02
(C(1)); 182.95 (C(4)). MS (EI, 15 eV), m/z (Irel (%)): 237 [M + 1]+
(11), 236 [M]+ (100), 222 (57), 218 (16), 207 (32), 194 (16).
5,8-Dihydroxy-2,6-dimethoxy-1,4-naphthoquinone (14). Yield
76%, m.p. 278—281 C (cf. Ref. 23: 275—280 C; Ref. 40:
295—296 C). IR (CDCl3), /cm–1: 3600—2200 (-OH), 3090,
2986, 2952, 2944, 2857, 1636, 1598, 1482, 1436, 1415, 1394, 1306,
1276, 1203, 1167, 1121, 1070. 1H NMR (CDCl3), : 3.97 (s, 6 H,
C(2)OMe, C(6)OMe); 6.37 (s, 2 H, H(3), H(7)); 13.09 (s, 2 H,
C(5)OH, C(8)OH). 13C NMR (CDCl3), : 56.79 (C(2)OMe,
C(6)OMe); 107.44 (C(3), C(7)); 108.70 (C(4a), C(8a)); 160.73
(C(2), C(6)); 164.99 (C(5), C(8)); 175.18 (C(1), C(4)). MS (EI,
15 eV), m/z (Irel (%)): 251 [M + 1]+ (2), 250 [M]+ (23), 232 (5),
221 (4), 220 (5), 208 (4), 207 (6), 206 (5), 202 (5), 179 (6), 149
(8), 121 (7), 88 (8), 69 (19), 59 (21), 46 (56), 45 (100), 44 (92),
43 (66), 42 (11), 41 (12), 32 (52).
6-Ethyl-3,5,8-trihydroxy-2-methoxy-1,4-naphthoquinone
(15). Yield 43%, heavy oil. IR (CDCl3), /cm–1: 3600—2200
(-OH), 3500 (-OH), 3400 (-OH), 2975, 2941, 2878, 1639,
1600, 1578, 1458, 1450, 1417, 1326, 1284, 1205, 1150, 1110, 1065.
1H NMR (CDCl3), : 1.25 (t, 3 H, Me, J = 7.6 Hz); 2.72 (dq,
2 H, CH2, J = 7.6 Hz, J = 1.0 Hz); 4.20 (s, 3 H, OMe); 6.82 (br.s,
1 H, C(3)OH); 7.09 (t, 1 H, H(7), J = 1.0 Hz); 12.03, 12.49 (both s,
1 H each, C(5)OH, C(8)OH). 13C NMR (CDCl3), : 12.76 (Me);
22.98 (CH2); 60.74 (C(2)OMe); 107.91 (C(8a)); 108.51 (C(4a));
128.36 (C(7)); 140.89 (C(2)); 142.90 (C(3)); 145.82 (C(6));
156.69 (C(5)); 158.09 (C(8)); 183.24 (C(4)); 183.85 (C(1)). MS
(EI, 70 eV), m/z (Irel (%)): 265 [M + 1]+ (16), 264 [M]+ (100),
263 [M – 1]+ (12), 249 (19), 246 (12), 231 (12), 221 (18), 218 (20),
217 (32), 203 (18), 193 (28), 149 (15), 136 (15), 91 (14), 53 (18),
43 (22), 41 (17), 32 (17). Found (%): C, 59.16; H, 4.68. C13H12O6.
Calculated (%): C, 59.09; H, 4.58.
1143, 1121, 1107, 1068, 1051. 1H NMR (CDCl3), : 1.25 (t, 3 H,
Me, J = 7.6 Hz); 2.73 (dq, 2 H, CH2, J = 7.6 Hz, J = 1.0 Hz);
4.11, 4.13 (both s, 3 H each, C(3)OMe, C(2)OMe); 7.06 (t, 1 H,
H(7), J = 1.0 Hz); 12.45, 12.89 (both s, 1 H each, C(8)OH,
C(5)OH). 13C NMR (CDCl3), : 12.77 (Me); 23.07 (CH2); 61.56
(C(3)OMe); 61.61 (C(2)OMe); 108.59 (C(8a)); 109.56 (C(4a));
127.23 (C(7)); 146.98 (C(6)); 147.68 (C(2)); 148.18 (C(3)); 157.84
(C(5)); 158.68 (C(8)); 183.38 (C(1)); 184.30 (C(4)). MS (EI,
70 eV), m/z (Irel (%)): 279 [M + 1]+ (15), 278 [M]+ (100), 277
[M – 1]+ (3), 264 (8), 263 (53), 261 (6), 260 (29), 249 (10), 248
(13), 245 (14), 233 (15), 217 (22), 207 (11), 149 (18), 136 (22),
77 (12), 53 (11), 32 (11).
O-Methylation of 2,5,8-trihydroxy-1,4-naphthoquinone
(naphthopurpurin) 3 with a solution of CH2N2 in Et2O. To a solu-
tion of substrate 3 (103 mg, 0.5 mmol) in MeOH, a saturated
solution of CH2N2 in anhydrous Et2O (10 mL) was added and
the mixture was kept at room temperature for 15 min. The vola-
tiles were removed in vacuo. The residue was subjected to silica
gel column chromatography. The column was first eluted with
hexane—acetone (35 : 1) to obtain product 18 (28 mg, 24%).
Subsequent elution with hexane—acetone (30 : 1) afforded
a mixture of compounds 20—22 (12 mg, 8%) in a ratio of
20 : 21 : 22 = 3 : 1.3 : 1. Further elution with hexane—acetone
(25 : 1) gave monomethoxy derivative 10 (26 mg, 24%) identical
to the sample described above. Finally, elution with hexane—ac-
etone (20 : 1) afforded compound 19 (4 mg, 3%).
5-Hydroxy-2,8-dimethoxy-1,4-naphthoquinone (18), yellow
heavy oil. 1H NMR (CDCl3), : 3.89, 3.97 (both s, 3 H each,
C(2)OMe, C(8)OMe); 6.06 (s, 1 H, H(3)); 7.29 (s, 2 H, H(6),
H(7)); 12.74 (s, 1 H, C(5)OH). 13C NMR (CDCl3), : 56.65
(C(2)OMe); 56.93 (C(8)OMe); 107.89 (C(3)); 114.01 (C(4a));
116.94 (C(8a)); 122.48 (C(7)); 127.53 (C(6)); 154.75 (C(8));
156.07 (C(5)); 161.74 (C(2)); 177.54 (C(1)); 190.69 (C(4)). MS
(EI, 70 eV), m/z (Irel (%)): 235 [M + 1]+ (12), 234 [M]+ (74),
220 [M + 1 – Me]+ (11), 219 [M – Me]+ (41), 205 (11), 191 (26),
189 (16), 32 (100). Found (%): C, 61.61; H, 4.35. C12H10O5.
Calculated (%): C, 61.54; H, 4.30.
5-Hydroxy-6,8-dimethoxy-1-methylnaphtho[2,3-d]pyrazole-
4,9-dione (22). 1H NMR (CDCl3), : 3.89, 3.96 (both s, 3 H each,
C(6)OMe, C(8)OMe); 4.31 (s, 3 H, N(1)Me); 6.64, 8.00 (both s,
1 H each, H(7), H(3)); 13.17 (s, 1 H, C(5)OH). 13C NMR
(CDCl3), : 39.32 (NMe); 56.55 (C(6)OMe); 61.26 (C(8)OMe);
105.22 (C(7)); 107.61 (C(4a)); 110.34 (C(8a)); 128.32 (C(3a));
130.84 (C(9a)); 137.36 (C(3)); 162.33 (C(8)); 162.71 (C(5));
163.32 (C(6)); 178.17 (C(9)); 179.73 (C(4)).
6-Ethyl-2,5,8-trihydroxy-3-methoxy-1,4-naphthoquinone
(16). Yield 31%, heavy oil. IR (CDCl3), /cm–1: 3600—2200
(-OH), 3491 (-OH), 3392 (-OH), 2973, 2945, 2859, 1651,
1602, 1583, 1455, 1422, 1393, 1324, 1278, 1198, 1154, 1107, 1035.
1H NMR (CDCl3), : 1.26 (t, 3 H, Me, J = 7.6 Hz); 2.74 (dq,
2 H, CH2, J = 7.6 Hz, J = 1.0 Hz); 4.18 (s, 3 H, OMe); 6.97 (br.s,
1 H, C(2)OH); 7.03 (t, 1 H, H(7), J = 1.0 Hz); 11.61 (br.s, 1 H,
C(8)OH); 12.99 (s, 1 H, C(5)OH). 13C NMR (CDCl3), : 12.74
(Me); 23.28 (CH2); 60.75 (C(3)OMe); 107.40 (C(8a)); 108.94
(C(4a)); 126.06 (C(7)); 140.61 (C(3)); 143.33 (C(2)); 148.50
(C(6)); 157.30 (C(5)); 157.57 (C(8)); 182.27 (C(1)); 184.75 (C(4)).
MS (EI, 70 eV), m/z (Irel (%)): 265 [M + 1]+ (13), 264 [M]+
(100), 263 [M – 1]+ (9), 249 (15), 246 (10), 231 (13), 221 (15),
218 (16), 217 (37), 203 (14), 193 (32). Found (%): C, 59.18;
H, 4.69. C13H12O6. Calculated (%): C, 59.09; H, 4.58.
5-Hydroxy-7,8-dimethoxy-1-methylnaphtho[2,3-d]pyrazole-
4,9-dione (21). 1H NMR (CDCl3), : 3.91, 3.95 (both s, 3 H each,
C(7)OMe, C(8)OMe); 4.35 (s, 3 H, N(1)Me); 6.69, 7.99 (both s,
1 H each, H(6), H(3)); 13.52 (s, 1 H, C(5)OH). 13C NMR
(CDCl3), : 39.45 (NMe); 56.66 (C(7)OMe); 61.18 (C(8)OMe);
106.00 (C(8a)); 106.57 (C(6)); 109.32 (C(4a)); 126.45 (C(3a));
131.15 (C(9a)); 136.25 (C(3)); 159.11 (C(8)); 160.74 (C(7)); 163.32
(C(5)); 176.02 (C(9)); 181.92 (C(4)).
5,8-Dihydroxy-7-methoxy-1-methylnaphtho[2,3-d]pyrazole-
1
4,9-dione (20). H NMR (CDCl3), : 3.99 (s, 3 H, C(7)OMe);
4.31 (s, 3 H, N(1)Me); 6.65, 8.05 (both s, 1 H each, H(6), H(3));
13.08, 13.46 (both s, 1 H each, C(8)OH, C(5)OH).
6-Ethyl-5,8-dihydroxy-2,3-dimethoxy-1,4-naphthoquinone
(17). Yield 71%, m.p. 69—71 C (cf. Ref. 56: 68—70 C). IR
(CDCl3), /cm–1: 3600—2200 (-OH), 2972, 2940, 2878, 2856,
1606, 1601, 1579, 1449, 1435, 1418, 1380, 1286, 1272, 1212, 1193,
5,8-Dihydroxy-1-methylnaphtho[2,3-d]pyrazole-4,9-dione
(19). M.p. 218—220 C. IR (CDCl3), /cm–1: 3550—2300
(-OH), 2956, 2928, 2865, 2856, 1624, 1617, 1576, 1530, 1462,
1453, 1399, 1377, 1335, 1306, 1287, 1254, 1239, 1205, 1183, 1161,